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Updated: Sep 1, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer
David Dora1, Christopher Rivard2, Hui Yu2
1Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Background:
SCLC is an aggressive malignancy where immunotherapies show limited efficacy. We aimed to characterize the SCLC microenvironment according to the expression patterns of SCLC subtype markers and novel immune checkpoints to identify therapeutic vulnerabilities.
Methods:
We included SCLC tissue samples from 219 surgically resected, limited-stage patients in this cross-sectional study. We performed immunohistochemistry for STING and MHCII, as well as for the novel subtype markers (ASCL1, NEUROD1, POU2F3, YAP1). Moreover, we assessed CD45 + , CD8 + and CD68 + immune cell infiltration.
Results:
36% of SCLC tumors showed significant stromal or intraepithelial CD45 + immune cell infiltration. These patients exhibited significantly increased overall survival (OS) (vs. patients with immune-deserted tumors). High CD8 expression was associated with increased median OS. We found STING expression on cancer-associated fibroblasts in the stroma and on T-cells and macrophages in both tumorous and stromal compartments. STING expression positively correlated with immune cell infiltration. Increased STING-positivity in tumor nests was an independent favorable prognosticator for OS. ASCL1 was the most frequently expressed subtype-specific protein. Concomitant expression of three or four subtype-defining markers was seen in 13.8% of the included samples, whereas 24.1% of the cases were classified as quadruple negative tumors. YAP1 expression was associated with increased immune infiltrates. Tumor cell MHCII expression positively correlated with immune cell infiltration and with STING- and YAP1 expressions.
Conclusions:
STING and MHCII are expressed in SCLC. The majority of immune-infiltrated SCLCs exhibit increased STING expression. Immune infiltration and STING expression are prognostic in limited-stage SCLC, making STING a potential therapeutic target.
Insights
Immune cell infiltration and STING expression are prognostic in limited-stage Small Cell Lung Cancer (SCLC). Increased STING positivity in tumors indicates better overall survival, suggesting STING as a potential therapeutic target for SCLC.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Small Cell Lung Cancer (SCLC) is an aggressive malignancy with limited efficacy of current immunotherapies.
- Characterizing the SCLC tumor microenvironment is crucial for identifying therapeutic vulnerabilities.
Purpose of the Study:
- To investigate the expression patterns of SCLC subtype markers and novel immune checkpoints.
- To identify potential therapeutic targets within the SCLC microenvironment.
Main Methods:
- Analysis of 219 surgically resected, limited-stage SCLC tissue samples.
- Immunohistochemistry for STING, MHCII, and SCLC subtype markers (ASCL1, NEUROD1, POU2F3, YAP1).
- Assessment of CD45+, CD8+, and CD68+ immune cell infiltration.
Main Results:
- 36% of SCLC tumors showed significant immune cell infiltration, correlating with increased overall survival (OS).
- High CD8 expression and STING expression in tumor nests were favorable prognosticators for OS.
- STING expression correlated positively with immune cell infiltration; YAP1 and MHCII expression also correlated with immune infiltrates.
Conclusions:
- STING and MHCII are expressed in SCLC, with increased STING in immune-infiltrated tumors.
- Immune infiltration and STING expression are prognostic indicators in limited-stage SCLC.
- STING represents a potential therapeutic target for SCLC treatment.
